Use of Elderly Donors in Liver Transplantation: A Paired-match Analysis at a Single Center

OBJECTIVE: To evaluate the use of elderly donors in liver transplantation (LT) and identify risk factors associated with a worse outcome. SUMMARY BACKGROUND DATA: Use of livers from very old donors could expand the donor pool but is not universally implemented. METHODS: This is a retrospective, single-center medical record review. From January 2001 to December 2014, 1354 LTs were performed. After exclusion of donors <18 years, ABO-incompatible LT, re-LT and UNOS 1 status patients, LT recipients were stratified into 2 groups based on donor age: 18-69 (n=692) vs. ≥70 years (n=515) then matched using a propensity score approach. Two groups were finally matched (young group = 448 cases; old group = 515 cases). RESULTS: The median (interquartile range [IQR]) follow-up was 5.0 (2.0-8.4) years. Comparing the 2 identified groups, no differences were observed regarding early retransplants (1.8 vs. 2.9; P = 0.3), HCV-related death (7.6 vs. 8.7%; P = 0.6), vascular (5.8 vs. 5.0%; P = 0.7), and biliary complications (16.5 vs. 18.6%; P = 0.4). On multivariate analysis, independent risk factors for graft loss were: HCV-positive recipient (HR = 2.1; 95% CI = 1.6-2.7; P < 0.001), donor age (HR = 1.0; 95% CI = 1.0-1.0; P < 0.001), cold ischemia time (HR = 1.0; 95% CI = 1.0-1.0; P = 0.042), and donor history of diabetes mellitus (HR = 1.48; 95% CI = 1.03-2.13; P = 0.036). CONCLUSIONS: Use of elderly donors is not associated per se with an increased risk of vascular and biliary complications. In the presence of cold ischemia time and diabetes mellitus, appropriate donor-to-recipient matching is warranted

Colorectal Cancer with Peritoneal Metastases: The Impact of the Results of PROPHYLOCHIP, COLOPEC, and PRODIGE 7 Trials on Peritoneal Disease Management

HIPEC is a potentially useful locoregional treatment combined with cytoreduction in patients with peritoneal colorectal metastases. Despite being widely used in several cancer centers around the world, its role had never been investigated before the results of three important RCTs appeared on this topic. The PRODIGE 7 trial clarified the role of oxaliplatin-based HIPEC in patients treated with radical surgery. Conversely, the PROPHYLOCHIP and the COLOPEC were designed to chair the role of HIPEC in patients at high risk of developing peritoneal metastases. Although all three trials demonstrated the relative ineffectiveness of HIPEC for treating or preventing peritoneal metastases, these results are not sufficient to abandon this technique. In addition to some criticisms relating to the design of the trials and their statistical value, the oxaliplatin-based HIPEC was found to be ineffective in preventing or treating peritoneal colorectal metastases, especially in patients already treated with systemic platinum-based chemotherapy. Several studies are ongoing investigating further HIPEC drugs and regimens. The review deeply discussed all the aspects and relapses of this new evidence

Platelets and Hepatocellular Cancer: Bridging the Bench to the Clinics

Growing interest is recently being focused on the role played by the platelets in favoring hepatocellular cancer (HCC) growth and dissemination. The present review reports in detail both the experimental and clinical evidence published on this topic. Several growth factors and angiogenic molecules specifically secreted by platelets are directly connected with tumor progression and neo-angiogenesis. Among them, we can list the platelet-derived growth factor, the vascular endothelial growth factor, the endothelial growth factor, and serotonin. Platelets are also involved in tumor spread, favoring endothelium permeabilization and tumor cells' extravasation and survival in the bloodstream. From the bench to the clinics, all of these aspects were also investigated in clinical series, showing an evident correlation between platelet count and size of HCC, tumor biological behavior, metastatic spread, and overall survival rates. Moreover, a better understanding of the mechanisms involved in the platelet-tumor axis represents a paramount aspect for optimizing both current tumor treatment and development of new therapeutic strategies against HCC

Platelets and hepatocellular cancer: Bridging the bench to the clinics

Growing interest is recently being focused on the role played by the platelets in favoring hepatocellular cancer (HCC) growth and dissemination. The present review reports in detail both the experimental and clinical evidence published on this topic. Several growth factors and angiogenic molecules specifically secreted by platelets are directly connected with tumor progression and neo-angiogenesis. Among them, we can list the platelet-derived growth factor, the vascular endothelial growth factor, the endothelial growth factor, and serotonin. Platelets are also involved in tumor spread, favoring endothelium permeabilization and tumor cells\u2019 extravasation and survival in the bloodstream. From the bench to the clinics, all of these aspects were also investigated in clinical series, showing an evident correlation between platelet count and size of HCC, tumor biological behavior, metastatic spread, and overall survival rates. Moreover, a better understanding of the mechanisms involved in the platelet\u2013tumor axis represents a paramount aspect for optimizing both current tumor treatment and development of new therapeutic strategies against HCC

Overview of prognostic systems for hepatocellular carcinoma and ITA.LI.CA external validation of MESH and CNLC classifications

Prognostic assessment in patients with HCC remains an extremely difficult clinical task due to the complexity of this cancer where tumour characteristics interact with degree of liver dysfunction, patient general health status, and a large span of available treatment options. Several prognostic systems have been proposed in the last three decades, both from the Asian and European/North American countries. Prognostic scores, such as the CLIP score and the recent MESH score, have been generated on a solid statistical basis from real life population data, while staging systems, such as the BCLC scheme and the recent CNLC classification, have been created by experts according to recent HCC prognostic evidences from the literature. A third category includes combined prognostic systems that can be used both as prognostic scores and staging systems. A recent example is the ITA.LI.CA prognostic system including either a prognostic score and a simplified staging system. This review focuses first on an overview of the main prognostic systems for HCC classified according to the above three categories, and, second, on a comprehensive description of the methodology required for a correct comparison between different systems in terms of prognostic performance. In this second section the main studies in the literature comparing different prognostic systems are described in detail. Lastly, a formal comparison between the last prognostic systems proposed for each of the above three categories is performed using a large Italian database including 6882 HCC patients in order to concretely apply the comparison rules previously described

Dual aortic and portal perfusion at procurement prevents ischaemic-type biliary lesions in liver transplantation when using octogenarian donors: a retrospective cohort study.

Several risk factors for ischaemic-type biliary lesions (ITBL) after liver transplantation (LT) have been identified, but the role of portal vein perfusion at graft procurement is still unclear. This was a prospective study on double aortic and portal perfusion (DP) of liver grafts stratified by donor's decade (<60 yo; 60-69 yo; 70-79 yo and >= 80 yo) versus similar historical cohorts of primary, adult grafts procured with single aortic perfusion (SP) only. The primary study aim was to assess the role of DP on the incidence of ITBL. There was no difference in the incidence of overall biliary complications according to procurement technique for recipients of grafts <80 years. A higher incidence of ITBL was observed for patients receiving grafts >= 80 years and perfused through the aorta only (1.9 vs. 13.4%; P = 0.008). When analysing octogenarian grafts, donor male gender (HR = 6.4; P = 0.001), haemodynamic instability (HR = 4.9; P = 0.008), and type-2 diabetes mellitus (DM2) (HR = 3.0; P = 0.03) were all independent risk factors for ITBL, while double perfusion at procurement (HR = 0.1; P = 0.04) and longer donor intensive care unit (ICU) stay (HR = 0.7; P = 0.04) were protective factors. Dual aortic and portal perfusion has the potential to reduce post-transplant ITBL incidence for recipients of octogenarian donor grafts. Larger series are needed to confirm this preliminary experience

Salvage of an octogenarian liver graft using normothermic perfusion. A case report

Liver transplantation with very old donors is safe, but is associated with an increased incidence of ischemic-type biliary lesions and delayed graft function. Normothermic machine perfusion (NMP) is a novel technique for preservation of liver grafts and has the potential to reduce ischemia-reperfusion injury. A case is reported here of a liver transplantation (LT) with a graft from an 83-year-old brain-dead donor. Procurement was with dual perfusion and en bloc, modified fast technique. Donor kidneys were not transplanted due to severe atherosclerosis and poor perfusion. The liver was shipped to the transplantation center and underwent NMP with a blood-based perfusate. During machine perfusion lactates decreased, vascular flow was stable, and bile production restored, and the graft was considered suitable for transplantation. The postoperative course was uneventful and 4 months after surgery the patient is in good clinical condition with normal liver function. To date, few LTs have been performed with NMP in humans, but its preliminary results are promising. NMP allows functional evaluation of the graft and possibly reduction of post-transplantation complications when extended-criteria donor grafts are used.Liver transplantation with very old donors is safe, but is associated with an increased incidence of ischemic-type biliary lesions and delayed graft function. Normothermic machine perfusion (NMP) is a novel technique for preservation of liver grafts and has the potential to reduce ischemia-reperfusion injury. A case is reported here of a liver transplantation (LT) with a graft from an 83-year-old brain-dead donor. Procurement was with dual perfusion and en bloc, modified fast technique. Donor kidneys were not transplanted due to severe atherosclerosis and poor perfusion. The liver was shipped to the transplantation center and underwent NMP with a blood-based perfusate. During machine perfusion lactates decreased, vascular flow was stable, and bile production restored, and the graft was considered suitable for transplantation. The postoperative course was uneventful and 4 months after surgery the patient is in good clinical condition with normal liver function. To date, few LTs have been performed with NMP in humans, but its preliminary results are promising. NMP allows functional evaluation of the graft and possibly reduction of post-transplantation complications when extended-criteria donor grafts are used

Sequential use of normothermic regional and ex-situ machine perfusion in DCD liver transplant

In Italy, 20 minutes of continuous, flat-line electrocardiogram are required for declaration of death. In the setting of organ donation after cardiocirculatory death (DCD), prolonged warm ischemia time prompted introduction of abdominal normothermic regional perfusion (NRP) followed by post-procurement, ex-situ machine perfusion. This was a retrospective review of DCD liver transplantations performed at two centers using sequential NRP and ex-situ machine perfusion. From January 2018 to April 2019, 34 DCD donors were evaluated. Three (8.8%) were discarded before NRP, 11 (32.4%) based on NRP parameters (n=1, 3.0%), liver macroscopic appearance at procurement and/or biopsy results (n=9, 26.5%), or severe macroangiopathy at back table evaluation (N=1, 3.0%). Twenty grafts (58.8%) (12 uncontrolled DCD, 8 controlled DCD) were considered eligible for LT, procured and perfused ex-situ (9 normothermic and 11 dual hypothermic machine perfusion). Eighteen (52.9%; 11 uncontrolled) were eventually transplanted. Median (IQR) no-flow time was 32.5 (30-39) minutes, while median functional-warm ischemia time was 52.5 (47-74) minutes (controlled DCD) and median low-flow time 112 (105-129) minutes (uncontrolled DCD). There was no primary non-function, while post-reperfusion syndrome occurred in 8 (44%) recipients. Early allograft dysfunction happened in 5 (28%) patients, while acute kidney injury in 5 (28%). After a median follow up of 15.1 (9.5-22.3) months, one case of ischemic-type biliary lesion and one patient death were reported. DCD liver transplantation is feasible even with the 20-minute no-touch rule. Strict normothermic regional perfusion and ex-situ machine perfusion selection criteria are needed to optimize post-operative results

Recurrence of hepatocellular carcinoma after direct acting antiviral treatment for hepatitis C virus infection: Literature review and risk analysis

Although studies suggest decreased incident hepatocellular carcinoma (HCC) after treatment with direct-acting antivirals (DAAs) for hepatitis C virus (HCV) infection, data are conflicting regarding risk and aggressiveness of recurrence in patients who have a history of treated HCC. This review analyses data available in literature in order to elucidate the impact of DAAs on the risk of HCC recurrence after successful treatment of the tumor. Overall 24 papers were identified. The available data cannot be considered definitive, but the initial alarmist data indicating an increased risk of recurrence have not been confirmed by most subsequent studies. The suggested aggressive pattern (rapid growth and vascular invasion) of tumor recurrence after DAAs still remains to be confirmed. Several limitations of the available studies were highlighted, and should drive future researches. The time-to-recurrence should be computed since the last HCC treatment and results stratified for cirrhosis and sustained viral response. Any comparison with historical series is of limited interest because of a number of biases affecting these studies and differences between enrolled patients. Prospective intention-to-treat analyses will be probably the best contribution to drive clinical practice, provided that a randomized trial can be difficult to design